Alkylnitrosoureas, because of their chemical simplicity and known catabolism as well as their ability to induce a high incidence of neurogenic tumor with precision, provides an excellent opportunity to study the basic problem of neoplastic transformation. It is proposed to examine the formation and removal of O6-alkylguanine as a possible DNA lesion crucial to neoplastic transformation. Attempts will be made to correlate alterations in DNA and RNA synthesis and the metabolism of nonhistone chromosomal proteins induced by methylnitrosourea and ethylnitrosourea with the carcinogenic potential of these compounds. Gene activation associated with tumor promotion will also be studied in relation to proteolytic derepression by the chromosomally associated serine-protease. Induction of the synthesis of helix destabilizing protein and its control at the level of transcription or translation will be investigated as the process responsive to both tumor promotor and chemical carcinogen. The precision of ethylnitrosourea in the neurogenic tumor induction will further be utilized in evaluating the role of nerve growth factor in suppression or regression of neoplastic transformation. The recently discovered thymic lymphoma production in rats exposed to methylnitrosourea will be studied in pursuit of establishing the tumor model for future biochemical, immunological and therapeutic investigations.